The proposed comparative study of hepatic microsomal mixed function oxidase systems induced by treatment of rats with polycyclic aryl compounds or with drugs aims at deciding whether the hemoprotein P-450 functions in the oxidative metabolism of polycyclic aromatic hydrocarbons as it does in the oxidative metabolism of drugs. The catalytic function of P-450 in the induced enzyme activity will be revealed by the photochemical action spectrum provided that the electron transfer to P-450 is adequate. Hence functionality of the flavoprotein-containing reducing system will be assayed. The mechanism of induction of P-450 by polycyclic arenes, which appears to differ from that by drugs, will be investigated with reference to time course, age and nutrition of animals and absorption and elimination of the inducer. To localize more precisely alterations in biochemical and biophysical properties of the multienzyme systems induced by aryl- and non-aryl compounds the available methods for resolving these systems and purifying their components will be evaluated and compared with a procedure developed in our laboratory. The methods to be applied for studying the interaction of P-450 with the other enzymatic components of the systems and with various substrates and ligands will include electron paramagnetic resonance spectrometry. The physical and chemical properties of the solubilized systems will be compared with those of the corresponding membrane-bound microsomal systems in order to assess to what extent the observed differences between aryl- and non-aryl induced P-450 systems can be attributed to changes in the heme, the protein moiety or the microenvironment of the membrane, the final goal being to determine in what way changes in the P-450 systems induced by polycyclic aromatic hydrocarbons and other xenobiotics are of significance in converting procarcinogens to carcinogens or in their inactivation.